Analysis of neurosteroid levels in attention deficit hyperactivity disorder.

Neurosteroids are important neuroactive substrates with demonstrated involvement in several neurophysiological and disease processes. Attention deficit hyperactivity disorder (ADHD) has been associated with dysregulation of the catecholaminergic and serotonergic systems, however its relationship to irregularities or changes in neurosteroid levels remains unknown. We examined the relationship between blood levels of dehydroepiandrosterone (DHEA), its principal precursor pregnenolone and its principal metabolite dehydroepiandrosterone sulphate (DHEAS) in 29 young male subjects aged 7-15 years with DSM-IV criteria of ADHD. Subjects were evaluated by a specially designed scale, following which patients were divided into two groups according to severity of symptomatology. Results indicated significant inverse correlations between clinical symptomatology and levels of DHEA and pregnenolone in the total group. These inverse correlations were particularly evident in the less severe group of subjects. Levels of DHEA and DHEAS were inversely correlated with the hyperactivity subscale. Furthermore, using median blood levels as a cut-off indicator, higher blood levels of DHEA and DHEAS were associated with fewer ADHD symptoms, in particular hyperactivity symptomatology. Our findings suggest a possible protective effect of various neurosteroids on the expression of ADHD symptomatology.

The influence of three months of methylphenidate treatment on platelet-poor plasma biogenic amine levels in boys with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is related to dysregulation in the activity of brain monoamines. The aim of the present study was to assess the impact of three months' methylphenidate (MPH) treatment on platelet-poor plasma (PPP) norepinephrine (NE), dopa and serotonin (5-HT) levels as well as on ADHD symptomatology. Three months of MPH treatment in 16 ADHD boys, aged 11.4 +/- 1.6 years, resulted in a significant reduction in PPP NE levels (p < 0.05). A tendency towards a reduction of PPP 5-HT and dopa levels was detected (p < 0.1 for both). The decrease in PPP biogenic amine levels after three months of MPH treatment was accompanied by a significant reduction in all psychometric characteristics of ADHD. This result indicates the possible role of overactivity of the noradrenergic system in the pathophysiology of ADHD and suggests that the MPH therapeutic action may be related to stimulant-induced inhibitory effect on the noradrenergic system. Copyright 2001 John Wiley & Sons, Ltd.

Circulatory levels of catecholamines, serotonin and lipids in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) may be associated with a dysregulation of the catecholaminergic and serotonergic systems. Furthermore, ADHD is frequently complicated by aggressive impulsive behaviour, which is suggested to be related to low serum cholesterol levels. We examined the relationship between blood serotonin, norepinephrine, dopa and lipid levels and the degree of hyperactivity, impulsiveness, lack of concentration, and aggressiveness in boys with ADHD of low and high severity as determined by a specially designed formulated scale based on the DSM-IV criteria for ADHD. No differences were noted between the groups in any of the peripheral biological parameters except blood serotonin, for which a tendency (P=0.08) towards lower levels was observed in the children with more severe disorder. We conclude that children with severe ADHD may have a different serotonin turnover compared to children with mild ADHD. These results may have implications for our understanding of the pathogenesis of ADHD, at least the more severe type.

Neuroleptic malignant syndrome associated with abrupt withdrawal of anticholinergic agents.

Neuroleptic malignant syndrome (NMS) is a severe side-effect of neuroleptic treatment. It is usually related to hypodopaminergic activity. A young schizophrenic patient who developed a typical episode of NMS during abrupt withdrawal of long-acting neuroleptic combined with anticholinergic treatment is described. NMS appeared following combined neuroleptic/ anticholinergic withdrawal and responded to procyclidine administration. The appearance of NMS after discontinuation of antidopaminergic treatment seems to be in conflict with the hypodopaminergic theory of this adverse effect. It is suggested that simultaneous withdrawal of both anticholinergic and neuroleptic medications, mainly long-acting neuroleptics, seems to be a risk factor for NMS.